PB2162: EVALUATION OF IMMUNE RECONSTITUTION IN MULTIPLE MYELOMA PATIENTS ON MAINTENANCE THERAPY WITH LENALIDOMIDE - THE ROLE OF HEAVYLITE CHAINS
Authors: Mariana Miranda, Rui Bergantim, Fernanda Trigo
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple Myeloma (MM) has been the focus of major advances and developments, both in therapy and in innovative methods of diagnosis and response evaluation. One of the pillars of current MM therapy are immunomodulatory drugs such as lenalidomide, used in first-line treatment and maintenance after auto-transplantation. These drugs have an excellent anti-tumor activity by inhibiting the growth of MM cells in the bone marrow, but also by promoting the function of immune effector cells. Thus, it becomes relevant to use disease assessment methods to characterize the patient’s immune status and understand the impact of disease and treatment on immunosuppression and immune reconstitution. The evaluation of HeavyLite chains (HLC) could be an important marker to assess the immune reconstitution of MM patients. The suppression of the uninvolved HLC pair (uHLC) is believed to have prognostic value and to reflect the patient’s immune reconstitution. Aims: Analyze the evolution of involved and uninvolved HLC of patients diagnosed with MM under maintenance therapy with lenalidomide for 12 months. Methods: Serum samples from 18 patients diagnosed with MM (11 male and 7 female) were evaluated at day 100 after autologous transplantation (D100) and after 1 year of maintenance with lenalidomide. Involved (iHLC) and uninvolved (uHLC) HLC levels were assessed. Immunoparesis (IP) was defined when uHLC values were lower than the assay reference values. SPSS version 28 software was used for statistical analysis of the data. Results: The isotypes of the patients evaluated were the following: IgG Kappa (n=8), IgG Lambda (n=6), IgA kappa (n=3) and IgA Lambda (n=1). 15 were in complete response (CR) and 3 were in very good partial response (VGPR) at D100. iHLC levels at D100 and after 1 year of treatment were higher in VGPR patients compared to CR patients, without statistical significance (D100 - median iHLC: 5.02 vs 3.11 g/L respectively; 12 months - median iHLC 8.45 vs 5.02 g/L). The uHLC values were similar in both groups and in both measurements (D100 – median uHLC: 3.68 vs 3.5 g/L; 12 months - median uHLC 4.78 vs 4.4 g/L). At D100 only 2 patients had PI. After 1 year of lenalidomide maintenance, 1 of these patients recovered from IP. There were no relevant infectious intercurrences during the evaluated period. Summary/Conclusion: This is an important result that confirms the efficacy of maintenance therapy with lenalidomide since the patients did not lose response and in one case there was even immunological recovery. Furthermore, it reflects the importance of controlling not only the involved but also the uninvolved HLC for a better distinction between patients with more immune dysregulation and with a potential worse prognosis. We must keep in mind that severe immunoparesis is an independent risk factor for bacteremia and early death, reinforcing the importance of selecting and evaluating HLC chain values in these specific patients. Keywords: Multiple myeloma, Immunomodulation